Genetic studies have revealed that genetic rearrangements resulting in loss of function, such as deletions, are the most frequent alterations in solid tumors. Chromosome translocations accompanied by oncogene activation, have, however, also been described frequently in soft tissues sarcomas. For example, in Ewing's sarcoma and in primitive neuroectodermal tumors (PNET), the EWS gene at band 22q12 fuses either with the FLI-1 gene at band 11q24 or with the ERG gene at band 21q22, leading to the formation of a chimeric transforming genes. Other examples include: the SYT-SSX gene fusion in synovial sarcomas with the t(X;18)(p11.2;q11.2) chromosome translocations; the TLS-CHOP fusion gene found in myxoid liposarcoma with t(12;16)(q13;p11); and the fusion of the PAX-3 homeotic gene with the FKHR gene in t(2;13)(q35;q14) translocations involved in alveolar rhabdomyosarcoma.
The molecular characterization of the t(1;17) and t(17;22) translocations in neurofibromatosis type 1 has led to the cloning of the NF1 gene, encoding neurofibromin, a protein that downregulates p21ras. Additional studies demonstrated that the NF1 gene is a tumor suppressor gene. In fact, mutations of the NF1 gene that cause familial neurofibromatosis, also occur in somatic cells and can lead to the development of tumors such as colon adenocarcinoma, myelodysplastic syndrome and anaplastic astrocytoma.
The characterization of genetic rearrangements associated with solid tumors is relevant to the diagnosis of disease, prognosis of likely outcome and determination of therapeutic action. The genetic basis for a tumorigenic phenotype indicates the nature of the tumor, its likely aggressiveness and its likelihood to respond to various modes of therapeutic intervention.
Accordingly, there is a need for reagents, kits and methods for screening tissue for genetic rearrangements involving the ALL-1 gene. There is a need for reagents, kits and methods for identifying solid tumors which contain genetic rearrangements involving the ALL-1 gene.